title: Effect of botanical immunomodulators on human CYP3A4 inhibition: implications for concurrent use as adjuvants in cancer therapy.
abstract: OBJECTIVE
  Many botanical immunomodulators are used as adjuvants along with cancer chemotherapy. However, information on the impact of concurrent administration of such botanicals on pharmacokinetics of chemotherapy agents is inadequate. This study investigates inhibitory activities of 3 popular botanical adjuvants: ASPARAGUS RACEMOSU: (root aqueous extract; ARE), WITHANIA SOMNIFER: (root aqueous extract; WSE), and TINOSPORA CORDIFOLI: (stem aqueous extract, TCE) on human CYP3A4 isoenzyme, responsible for metabolism of several chemotherapy agents.
  
  
  METHODS
  . Testosterone 6-β hydroxylation was monitored using high-performance liquid chromatography as an indicator of CYP3A4 catalytic activities. Ketoconazole (positive control) and extracts were studied at their in vivo-relevant concentrations.
  
  
  RESULTS
  TCE showed mild inhibition while no significant inhibitory activities were observed in WSE and ARE. TCE was further fractionated to obtain polar and nonpolar fractions. The nonpolar fraction showed significant CYP3A4 inhibition with IC50 13.06 ± 1.38 µg/mL. Major constituents of nonpolar fraction were identified using HPLC-DAD-MS profiling as berberine, jatrorrhizine, and palmatine, which showed IC50 values as 6.25 ± 0.30, 15.18 ± 1.59, and 15.53 ± 1.89 µg/mL, respectively.
  
  
  CONCLUSIONS
  Our findings suggest that constituents of TCE extract especially protoberberine alkaloids have the potential to interact with cancer chemotherapy agents that are metabolized by CYP3A4 in vivo.
authors.affiliation: Serum Institute of India Research Foundation, Hadapsar, Pune, India.
authors.forename: Dada
authors.initials: D
authors.lastname: Patil
authors.forename: Manish
authors.initials: M
authors.lastname: Gautam
authors.forename: Sunil
authors.initials: S
authors.lastname: Gairola
authors.forename: Suresh
authors.initials: S
authors.lastname: Jadhav
authors.forename: Bhushan
authors.initials: B
authors.lastname: Patwardhan
mesh_terms: D027761:Asparagus Plant / Q000737:chemistry; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D031610:Tinospora / Q000737:chemistry; D032341:Withania / Q000737:chemistry
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D007155:Immunologic Factors; D010936:Plant Extracts; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human
keywords: Asparagus racemosus; CYP3A4 inhibition; Tinospora cordifolia; Withania somnifera; botanical immunomodulators; cancer adjuvant; herb–drug interactions